OpenOnco · Treatment Plan

Treatment plan — Glioblastoma

PLAN-GBM-NEWLY-001-V1 · v1 · 2026-09-09

Patient

GBM-NEWLY-001 · Algorithm: ALGO-GBM-NEWLY-DIAGNOSED-1L

DiagnosisGlioblastoma

MOH / ICD-10C71

ICD-O-39440/3; C71

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
ESCAT: clinical review pendingBIO-MGMT-METHYLATION	MGMT promoter methylation (positive vs unmethylated; ~40% of newly-diagnosed glioblastoma IDH-WT)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Better Outcome) Trial or research option SRC-CIVIC: Level E (Supports, Sensitivity/Response)	MGMT promoter methylation in IDH-WT glioblastoma is the strongest validated predictor of temozolomide benefit (Stupp NEJM 2005 / 2009 long-term — methylated patients derive ~2x OS benefit from RT+TMZ vs RT alone). Standard 1L for newly-diagnosed GBM remains Stupp protocol (concurrent RT + temozolomide → 6 cycles adjuvant TMZ) per SRC-NCCN-CNS-2025, SRC-EANO-GBM-2024 — but methylation status drives intensification decisions: in elderly MGMT-methylated patients, hypofractionated RT + TMZ (Perry NEJM 2017) is preferred, while elderly MGMT-unmethylated patients can receive RT alone with much smaller TMZ benefit. CeTeG/NOA-09 (Herrlinger Lancet 2019) showed lomustine + TMZ + RT may extend OS in newly-diagnosed MGMT- methylated GBM but is not standard worldwide.	Stupp protocol: concurrent RT + temozolomide → 6 cycles adjuvant TMZ (1L MGMT-methylated GBM per SRC-NCCN-CNS-2025, SRC-EANO-GBM-2024) hypofractionated RT + TMZ (elderly ≥65y MGMT-methylated per SRC-EANO-GBM-2024) lomustine + TMZ + RT (alternative MGMT-methylated 1L per CeTeG/NOA-09 — listed as option in SRC-EANO-GBM-2024)	SRC-NCCN-CNS-2025 SRC-EANO-GBM-2024

⚠️ Not included in plan

Biomarker	Status
BIO-IDH-MUTATION	BIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-GBM-NEWLY-DIAGNOSED-STUPP

Regimen

Stupp protocol — Temozolomide concurrent + adjuvant

Drugs + NSZU

Temozolomide (DRUG-TEMOZOLOMIDE) Concurrent: 75 mg/m² PO daily during RT 6 weeks; Adjuvant: 150 mg/m² PO days 1-5 cycle 1 (escalate to 200 if tolerated) every 28 days × 6 cycles · Concurrent daily × 42 days then 4-week break then adjuvant cycles 1-6 · PO ✓ NSZU covered

Reason

Provisional current-line default from ALGO-GBM-NEWLY-DIAGNOSED-1L: step 1 did not select a treatment branch. IDH-mutant glioma grade 4: not GBM per WHO 2021. Manage as astrocytoma IDH-mutant (vorasidenib INDIGO). Separate disease pathway.

Other current-line alternatives (2 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

Indication

IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ

Regimen

Temozolomide monotherapy

Drugs + NSZU

Temozolomide (DRUG-TEMOZOLOMIDE) ✓ NSZU covered

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication: IND-GBM-NEWLY-DIAGNOSED-ELDERLY-HYPORT
Regimen: Hypofractionated radiotherapy for GBM
Reason: Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-IDH-MUTATION	IDH1/IDH2 mutation	Critical	histology	CSD Lab ✓ (code TBC)	all tracks
TEST-MGMT-METHYLATION	MGMT methylation	Critical	histology	CSD Lab ✓ (code TBC)	all tracks
TEST-MRI-BRAIN-CONTRAST	MRI brain with contrast	Standard	imaging	—	all tracks
TEST-NGS-COMPREHENSIVE	Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes)	Desired	histology	CSD Lab: M065	desired (standard)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Symptomatic raised intracranial pressure / mass effect in glioblastoma: declining GCS, new focal deficit, papilledema, midline shift on imaging, or seizure cluster. Mandates immediate neurosurgical / corticosteroid intervention BEFORE oncologic systemic therapy.
Mass effect emergency — dexamethasone 8-16 mg IV stat, neurosurgical consult for resection / debulking / VP shunt. Anti-epileptics for seizure cluster (levetiracetam preferred — no enzyme induction vs older AEDs that interfere with TMZ…
RF-GBM-INTRACRANIAL-PRESSURE-EMERGENCYSRC-NCCN-CNS-2025SRC-EANO-GBM-2024
Glioblastoma progression on or after first-line Stupp regimen: MRI evidence of true progression (RANO criteria — distinguished from pseudoprogression by serial imaging / advanced techniques), early recurrence <6 months post-RT (often pseudoprogression — repeat MRI at 4-8 weeks before re-treatment decision), or distant new lesion. Routes from upfront Stupp to recurrent-GBM algorithm (re-resection + bevacizumab / TTF / regorafenib / lomustine / re-irradiation).
Pseudoprogression occurs in ~30% post-Stupp at 3 mo MRI — does not represent true tumor growth (treatment-related inflammation / radiation effect); RANO criteria require either second confirmatory MRI or outside-RT-field new disease…
RF-GBM-TRANSFORMATION-PROGRESSIONSRC-NCCN-CNS-2025SRC-EANO-GBM-2024

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-GBM-NEWLY-DIAGNOSED-STUPP)

Do NOT delay starting RT beyond 6 weeks post-resection
Do NOT skip MGMT testing — defines elderly (≥70) regimen choice
Do NOT skip PJP prophylaxis (universal lymphopenia → opportunistic infection)
Do NOT use enzyme-inducing AEDs (phenytoin, carbamazepine) — accelerate TMZ clearance; use levetiracetam

Standard plan (IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ)

Do NOT use TMZ alone in MGMT-unmethylated GBM ≥70 — minimal benefit; prefer hypofractionated RT
Do NOT use full Stupp (60 Gy/30 fx) in patients ≥70 or KPS <60 — excessive toxicity
Do NOT skip MGMT testing before choosing TMZ vs RT — this is the key biomarker in elderly
Do NOT skip PJP prophylaxis (co-trimoxazole) — lymphopenia risk applies to TMZ mono too

Standard plan (IND-GBM-NEWLY-DIAGNOSED-ELDERLY-HYPORT)

Do NOT use full Stupp 60 Gy/30 fx in patients ≥70 or KPS <60 — unacceptable toxicity in elderly
Do NOT omit TMZ without first checking MGMT status — methylated patients benefit significantly
Do NOT skip MGMT testing — drives concurrent TMZ decision
Do NOT start RT without post-resection MRI (within 48h of surgery)
Do NOT delay RT beyond 6 weeks post-surgery

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Stupp protocol — Temozolomide concurrent + adjuvant

28-day cycles × Concurrent phase 6 weeks + adjuvant 6 cycles (~7 months total)

Standard plan

Induction · Temozolomide monotherapy

28-day cycles × Until progression or unacceptable toxicity; schedule per GBM protocol

MDT brief

MDT talk tree (1 steps)

#	Owner	Topic	Action
1	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Skills (recommended) — for consideration (1)

Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.

Biomarker coverage: 1/1 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-CASCADE-LFS-FDR-POSITIVE, RF-GBM-FRAILTY-AGE, RF-GBM-HIGH-RISK-BIOLOGY, RF-GBM-INFECTION-SCREENING, RF-GBM-TRANSFORMATION-PROGRESSION, RF-IATROGENIC-CRANIAL-RT-LATE-PREVENTION, RF-LI-FRAUMENI-FAMILY-HISTORY-SUSPICION

Technical MDT skill metadata (1/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-CCTG-CE6-PERRY-2017: Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma (2017)
SRC-EANO-GBM-2024: EANO Guidelines on Diagnosis and Treatment of Diffuse Gliomas of Adulthood (2024 update)
SRC-NCCN-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)
SRC-NORDIC-GBM-MALMSTROM-2012: Temozolomide versus Standard 6-Week Radiotherapy versus Hypofractionated Radiotherapy in Patients Older than 60 Years with Glioblastoma (2012)

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-09-09.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT07627334	Personalized Targeted Glioblastoma Therapies by ex Vivo Drug Screening: Advanced Brain Tumor TheRApy Clinical Trial In Patients Scheduled for shOrt Course radiatioN	NA	RECRUITING	Medical University of Vienna	—	Small N (<50) Single country
NCT05686798	Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.	PHASE1	RECRUITING	Henry Ford Health System	—	Phase 1 only Small N (<50) Single country
NCT06926075	Early Phase Study of KESONOTIDE™in Participants With Solid Tumours	PHASE1 / PHASE2	RECRUITING	Filamon LTD	—	Single country
NCT06186401	Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells	PHASE1	RECRUITING	Hideho Okada, MD, PhD	—	Phase 1 only Small N (<50) Single country
NCT05303519	SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)	PHASE3	RECRUITING	Nuvation Bio Inc.	—	Surrogate endpoint only
NCT07179328	Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy	PHASE1	RECRUITING	Sunnybrook Health Sciences Centre	—	Phase 1 only Small N (<50) Single country
NCT05864534	Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma	PHASE2	RECRUITING	Northwestern University	—	Small N (<50) Single country
NCT07708961	Temozolomide, With or Without WSD0922-FU, for the Treatment of EGFR-Mutant, IDH-Wildtype Glioblastoma	PHASE2	RECRUITING	Mayo Clinic	—	Surrogate endpoint only Single country
NCT06161974	Study of Olutasidenib and Temozolomide in HGG	PHASE2	RECRUITING	Rigel Pharmaceuticals	—	Surrogate endpoint only
NCT05083754	Carmustine Wafer in Combination With Retifanlimab and Radiation With/Without Temozolomide in Subjects With Glioblastoma	PHASE1	RECRUITING	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	—	Phase 1 only Single country

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Standard plan Stupp protocol — Temozolomide concurrent + adjuvant (REG-STUPP-TMZ)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Temozolomide monotherapy (REG-TMZ-MONO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Hypofractionated radiotherapy for GBM (REG-HYPOFRACTIONATED-RT-GBM) No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Trial · NCT07627334 Personalized Targeted Glioblastoma Therapies by ex Vivo Drug Screening: Advanced Brain Tumor TheRApy Clinical Trial In Patients Scheduled for shOrt Course radiatioN No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05686798 Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06926075 Early Phase Study of KESONOTIDE™in Participants With Solid Tumours No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06186401 Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05303519 SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07179328 Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05864534 Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07708961 Temozolomide, With or Without WSD0922-FU, for the Treatment of EGFR-Mutant, IDH-Wildtype Glioblastoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06161974 Study of Olutasidenib and Temozolomide in HGG No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05083754 Carmustine Wafer in Combination With Retifanlimab and Radiation With/Without Temozolomide in Subjects With Glioblastoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-09-09.

plan_id: PLAN-GBM-NEWLY-001-V1 | version: 1 | generated: 2026-09-09T12:26:41.453724+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.